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61.
Rebecca S. Hofford Tanner J. Euston Rashaun S. Wilson Katherine R. Meckel Emily G. Peck Arthur Godino Joseph A. Landry Erin S. Calipari TuKiet T. Lam Drew D. Kiraly 《The Journal of neuroscience》2021,41(7):1553
Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no Food and Drug Administration (FDA)-approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Male Sprague Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multiregion discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.SIGNIFICANCE STATEMENT Pharmacological treatments for psychostimulant use disorder are desperately needed, especially given the disease''s chronic, relapsing nature. However, there are currently no Food and Drug Administration (FDA)-approved pharmacotherapies. Emerging evidence suggests that targeting the immune system may be a viable translational research strategy; preclinical studies have found that the neuroactive cytokine granulocyte-colony stimulating factor (G-CSF) alters cocaine reward and reinforcement and can enhance cognitive flexibility. Given this basis of evidence we studied the effects of G-CSF treatment on extinction and reinstatement of cocaine seeking. We find that administration of G-CSF accelerates extinction and reduces cue-induced drug seeking after cocaine self-administration. In addition, G-CSF leads to downregulation of synaptic glutamatergic proteins in medial prefrontal cortex (mPFC), suggesting that G-CSF influences drug seeking via glutamatergic mechanisms. 相似文献
62.
A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty.
Nineteen boys with true isolated growth hormone deficiency developed the first stages of puberty at an average bone age of 12.0"years" (Tanner Whitehouse Method 2, RUS score). The average chronological age was 15.0 years. Seven similar girls entered puberty at 10.9"years" in bone age and 13.7 years in chronological age. The means and ranges of bone age at beginning of puberty of these patients are very close to those of normal children. 相似文献
63.
The presentation of the World Health Organization (WHO)’s roadmap for neglected tropical diseases (NTDs) in January 2012 raised optimism that many NTDs can indeed be eliminated. To make this happen, the endemic, often low-income countries with still heavy NTD burdens must substantially strengthen their health systems. In particular, they need not only to apply validated, highly sensitive diagnostic tools and sustainable effective control approaches for treatment and transmission control, but also to participate in the development and use of surveillance–response schemes to ensure that progress made also is consolidated and sustained. Surveillance followed-up by public health actions consisting of response packages tailored to interruption of transmission in different settings will help to effectively achieve the disease control/elimination goals by 2020, as anticipated by the WHO roadmap. Risk-mapping geared at detection of transmission hotspots by means of geospatial and other dynamic approaches facilitates decision-making at the technical as well as the political level. Surveillance should thus be conceived and developed as an intervention approach and at the same time function as an early warning system for the potential re-emergence of endemic infections as well as for new, rapidly spread epidemics and pandemics. 相似文献
64.
Preliminary Data from Community Aging in Place,Advancing Better Living for Elders,a Patient‐Directed,Team‐Based Intervention to Improve Physical Function and Decrease Nursing Home Utilization: The First 100 Individuals to Complete a Centers for Medicare and Medicaid Services Innovation Project 下载免费PDF全文
Sarah L. Szanton PhD Jennifer L. Wolff PhD Bruce Leff MD Laken Roberts MPH Roland J. Thorpe PhD Elizabeth K. Tanner PhD Cynthia M. Boyd MD Qian‐Li Xue PhD Jack Guralnik PhD David Bishai PhD Laura N. Gitlin PhD 《Journal of the American Geriatrics Society》2015,63(2):371-374
Current medical models frequently overlook functional limitations and the home environment even though they partially determine healthcare usage and quality of life. The Centers for Medicare and Medicaid Services (CMS) Innovation Center funds projects that have potential to affect the “triple aim,” a framework for decreasing costs while improving health and quality of life. This article presents preliminary data from Community Aging in Place, Advancing Better Living for Elders (CAPABLE), a model funded by the CMS Innovation Center and designed to overcome the functional and home environmental barriers of older adults. CAPABLE is a patient‐directed, team‐based intervention comprising an occupational therapist, a registered nurse, and a handyman to decrease hospitalization and nursing home usage of community‐dwelling older adults with functional limitations who are dually eligible for Medicare and Medicaid. Activity of daily living limitations improved in 79% of the first 100 people who completed the intervention. Preliminary findings of this novel intervention may have implications for other older adults with functional limitations. 相似文献
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66.
Stewart JD Marchan R Lesjak MS Lambert J Hergenroeder R Ellis JK Lau CH Keun HC Schmitz G Schiller J Eibisch M Hedberg C Waldmann H Lausch E Tanner B Sehouli J Sagemueller J Staude H Steiner E Hengstler JG 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):8155-8160
Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan-Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention. 相似文献
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69.
Alexander Breitenstein Susanna H. M. Sluka Alexander Akhmedov Simona Stivala Jan Steffel Giovanni G. Camici Huy H. Riem Hans-Jurg Beer Jan-Dirk Studt Firat Duru Thomas F. Luscher Felix C. Tanner 《Basic research in cardiology》2012,107(6):1-8
Dronedarone has been associated with a reduced number of first hospitalisation due to acute coronary syndromes. Whether this is only due to the reduction in ventricular heart rate and blood pressure or whether other effects of dronedarone may be involved is currently elusive. This study was designed to investigate the role of dronedarone in arterial thrombus formation. C57Bl/6 mice were treated with dronedarone and arterial thrombosis was investigated using a mouse photochemical injury model. Dronedarone inhibited carotid artery thrombus formation in vivo (P?<?0.05). Thrombin- and collagen-induced platelet aggregation was impaired in dronedarone-treated mice (P?<?0.05), and expression of plasminogen activator inhibitor-1 (PAI1), an inhibitor of the fibrinolytic system, was reduced in the arterial wall (P?<?0.05). In contrast, the level of tissue factor (TF), the main trigger of the coagulation cascade, and that of its physiological inhibitor, TF pathway inhibitor, did not differ. Similarly, coagulation times as measured by prothrombin time and activated partial thromboplastin time were comparable between the two groups. Dronedarone inhibits thrombus formation in vivo through inhibition of platelet aggregation and PAI1 expression. This effect occurs within the range of dronedarone concentrations measured in patients, and may represent a beneficial pleiotropic effect of this drug. 相似文献
70.
Diane Mullins Eileen Daly Andrew Simmons Felix Beacher Catherine ML Foy Simon Lovestone Brian Hallahan Kieran C Murphy Declan G Murphy 《Journal of Neurodevelopmental Disorders》2013,5(1):19